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Diabetes downregulates the antimicrobial peptide psoriasin and increases E. coli burden in the urinary bladder

Author

Listed:
  • Soumitra Mohanty

    (Karolinska Institutet
    Karolinska University Hospital)

  • Witchuda Kamolvit

    (Karolinska Institutet
    Karolinska University Hospital)

  • Andrea Scheffschick

    (Department of Medicine)

  • Anneli Björklund

    (Center for Diabetes, Academic Specialist Center, Stockholm County Council
    Karolinska Institutet)

  • Jonas Tovi

    (Capio Health Care Center)

  • Alexander Espinosa

    (Department of Medicine)

  • Kerstin Brismar

    (Karolinska Institutet)

  • Thomas Nyström

    (Division of Internal Medicine, Unit for Diabetes Research, Karolinska Institutet, South Hospital)

  • Jens M. Schröder

    (University Hospital Schleswig-Holstein)

  • Claes-Göran Östenson

    (Karolinska Institutet)

  • Pontus Aspenström

    (Uppsala University)

  • Hanna Brauner

    (Department of Medicine
    Karolinska University Hospital)

  • Annelie Brauner

    (Karolinska Institutet
    Karolinska University Hospital)

Abstract

Diabetes is known to increase susceptibility to infections, partly due to impaired granulocyte function and changes in the innate immunity. Here, we investigate the effect of diabetes, and high glucose on the expression of the antimicrobial peptide, psoriasin and the putative consequences for E. coli urinary tract infection. Blood, urine, and urine exfoliated cells from patients are studied. The influence of glucose and insulin is examined during hyperglycemic clamps in individuals with prediabetes and in euglycemic hyperinsulinemic clamped patients with type 1 diabetes. Important findings are confirmed in vivo in type 2 diabetic mice and verified in human uroepithelial cell lines. High glucose concentrations induce lower psoriasin levels and impair epithelial barrier function together with altering cell membrane proteins and cytoskeletal elements, resulting in increasing bacterial burden. Estradiol treatment restores the cellular function with increasing psoriasin and bacterial killing in uroepithelial cells, confirming its importance during urinary tract infection in hyperglycemia. In conclusion, our findings present the effects and underlying mechanisms of high glucose compromising innate immunity.

Suggested Citation

  • Soumitra Mohanty & Witchuda Kamolvit & Andrea Scheffschick & Anneli Björklund & Jonas Tovi & Alexander Espinosa & Kerstin Brismar & Thomas Nyström & Jens M. Schröder & Claes-Göran Östenson & Pontus As, 2022. "Diabetes downregulates the antimicrobial peptide psoriasin and increases E. coli burden in the urinary bladder," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32636-y
    DOI: 10.1038/s41467-022-32636-y
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    References listed on IDEAS

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    1. Bjoern O. Schroeder & Zhihong Wu & Sabine Nuding & Sandra Groscurth & Moritz Marcinowski & Julia Beisner & Johannes Buchner & Martin Schaller & Eduard F. Stange & Jan Wehkamp, 2011. "Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1," Nature, Nature, vol. 469(7330), pages 419-423, January.
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